Resurrecting the mammoth? New research raises the prospect

The star of the ancient DNA world has, so far, been the Neanderthal, presumably because it can tell us things about ourselves. But Neanderthal DNA is, unfortunately, in absolutely terrible shape; when sequencing with samples from Neanderthal bones, the vast majority of DNA that comes out is bacterial. As it turns out, however, there is one extinct species that has extraordinarily well-preserved DNA, and it's well on its way to having its genome completed: the mammoth.

A substantial number of mammoths have been discovered preserved in permafrost, and even though the DNA has degraded during the freeze-thaw cycles that put them there, it's far better than bones that have been sitting at environmental temperatures for longer time spans. The other big benefit of using mammoth DNA is that researchers can get rid of much of the contamination by means of a purification technique that wipes the bacterial DNA off mammoth hair shafts without damaging ancient DNA within.

S.C. Schuster

The net result is that, out of over 4 Gigabases worth of DNA sequence obtained by the authors of a new paper in Nature, about 80 percent came from the mammoth; in the case of one individual, that number went up over 90 percent. Given that elephants have relatively large genomes—roughly a Gigabase larger than the human genome—they estimate that they have now sequenced over 70 percent of the mammoth genome.

Comparisons with the partially completed elephant genome revealed few surprises. Despite having diverged from a common ancestor about the same time humans and chimps did, the mammoth and elephant differ about half as much as we do from the chimps. Differences in some protein coding genes were apparent but, without a detailed understanding of elephant biology, the significance of these is difficult to judge.

What the results do make clear is that there's essentially nothing but a bit of time and money between us and the complete genome of an extinct species. We still only have a draft version of the elephant, and we'd want to have that done in order to make sense of the mammoth sequence. But, with that in hand, we can easily piece the mammoth sequence together; indeed, we could probably complete the sequences of several mammoths.

Resurrecting the mammoth

Given that the genome is often called the blueprint for an organism, Nature took the liberty of commissioning an evaluation of what it would take to rebuild the mammoth using that blueprint. The challenge is enormous: each one of the mammoth's chromosomes are likely to be over 100 Megabases; the average surviving fragment of DNA is under 200 bases long.

So the piece suggests starting from scratch, using a process similar to the one that constructed the first artificial genome. Unfortunately, that bacterial genome is about three orders of magnitude smaller than a single mammoth chromosome, and the techniques used are simply unlikely to scale. Mammoths also had dozens of chromosomes, and we'd need to get two copies of each into a single cell, safely encapsulated in a nucleus. We've got techniques that work for some of this, but we've never tried any of them on a task approaching this scale.

Assuming we have two full sets of mammoth chromosomes together in a single nucleus, advances in stem cell research suggest we could reset them to an embryonic state using molecular tools. Unfortunately, the effort would run into problems on the macro scale. It would obviously be best to do this with elephants, both as egg donors and surrogates. But, apparently thanks to an aquatic lifestyle in the elephant's evolutionary past, they have a baroque reproductive tract and an internal organ arrangement that makes laparoscopy a non-starter.

There are a host of other issues that are relatively minor in scale—we'd need a Y chromosome and sequence from enough individuals to create a diverse breeding population—but resurrecting the mammoth faces some technological obstacles that we haven't yet even started to try to overcome. A more likely solution, Nature concludes, would be to identify the regions that have diverged most significantly between elephants and mammoths, and engineer the mammoth equivalent back into an elephant. Depending how well we can identify these, the mammophant that we produce may be at least physically indistinguishable from artists' renderings we're all familiar with.

The article quotes one of the researchers leading the efforts to sequence the Neanderthal genome, Svante Paabo, as saying he doesn't expect to see anything more than a mammophant in his lifetime. Of course, Paabo's in his 50s, and I'd imagine that, in his 20s, he wouldn't have expected to see a Neanderthal genome completed in his lifetime. He's now doing just that.